ASYMMETRIC SYNTHESIS OF 1,3-POLYOLS VIA HYDROSILATION

通过硅氢化不对称合成 1,3-多元醇

• 批准号: 6385237
• 负责人: CHRISTOPHER S STRAUB
• 金额: $ 3.48万
• 依托单位: UNIVERSITY OF TEXAS AT AUSTIN
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6385237
• 关键词: allyl compound; biological products; chemical synthesis; drug design /synthesis /production; polyhydroxy compound; silicon compounds; stereochemistry

The proposed research explores a novel methodology for the synthesis of 1,3-diol and 1,3,5-triol functionalities via the intramolecular hydrosilation of homoallylic alcohols. Alkene facial selectivity is afforded by the use of a chiral auxiliary (aC2 symmetric binaphthol) attached to the silicon atom of the starting material. It is proposed that the chiral auxiliary will then be able to be further utilized in relaying stereochemical information throughout the product in subsequent transformations. Thus through further functionalization and manipulation 1,3-polyol functionalities should be produced. In such a way, it is proposed that the chiral auxiliary can control the absolute stereochemistry of three centers before being cleaved from the product and recycled. The importance of 1,3-polyols is born out in their vast presence in the natural product world. Several antibiotic, anti-tumor and immunosuppressant compounds contain this functionality. One such compound, (-) discodermolide, contains three 1,3,5-triol units, one of which should be accessible using the proposed methodology. To further explore the scope of silicon tethered methodology, it is proposed that all three building blocks be made using variations of the hydrosilation methodology, and an important connection in making the backbone of the natural product be performed using a silicon tethered alkene ring closing metathesis protocol.

该研究探索了一种通过高烯丙醇分子内硅氢化反应合成1，3-二醇和1，3，5-三醇官能团的新方法。通过使用连接到起始材料的硅原子的手性助剂（aC 2对称联萘）来提供烯烃面选择性。有人提出，手性助剂，然后将能够进一步利用在中继立体化学信息在整个产品在随后的转换。因此，通过进一步的官能化和操作，应产生1，3-多元醇官能度。通过这种方式，提出了手性助剂在从产物中裂解并再循环之前可以控制三个中心的绝对立体化学。1，3-多元醇的重要性体现在其在天然产品世界中的广泛存在。几种抗生素、抗肿瘤和免疫抑制剂化合物都具有这种功能。一种这样的化合物，（-）discodermolide，含有三个1，3，5-三醇单元，其中之一应该是使用所提出的方法。为了进一步探索硅系方法的范围，提出了使用硅氢化方法的变化来制造所有三个构件，并且使用硅系烯烃闭环复分解方案来进行制造天然产物的主链的重要连接。